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Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis.


ABSTRACT: Chronic pancreatitis is a persistent inflammatory disease of the pancreas, in which the digestive protease trypsin has a fundamental pathogenetic role. Here we have analyzed the gene encoding the trypsin-degrading enzyme chymotrypsin C (CTRC) in German subjects with idiopathic or hereditary chronic pancreatitis. Two alterations in this gene, p.R254W and p.K247_R254del, were significantly overrepresented in the pancreatitis group, being present in 30 of 901 (3.3%) affected individuals but only 21 of 2,804 (0.7%) controls (odds ratio (OR) = 4.6; confidence interval (CI) = 2.6-8.0; P = 1.3 x 10(-7)). A replication study identified these two variants in 10 of 348 (2.9%) individuals with alcoholic chronic pancreatitis but only 3 of 432 (0.7%) subjects with alcoholic liver disease (OR = 4.2; CI = 1.2-15.5; P = 0.02). CTRC variants were also found in 10 of 71 (14.1%) Indian subjects with tropical pancreatitis but only 1 of 84 (1.2%) healthy controls (OR = 13.6; CI = 1.7-109.2; P = 0.0028). Functional analysis of the CTRC variants showed impaired activity and/or reduced secretion. The results indicate that loss-of-function alterations in CTRC predispose to pancreatitis by diminishing its protective trypsin-degrading activity.

SUBMITTER: Rosendahl J 

PROVIDER: S-EPMC2650829 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis.

Rosendahl Jonas J   Witt Heiko H   Szmola Richárd R   Bhatia Eesh E   Ozsvári Béla B   Landt Olfert O   Schulz Hans-Ulrich HU   Gress Thomas M TM   Pfützer Roland R   Löhr Matthias M   Kovacs Peter P   Blüher Matthias M   Stumvoll Michael M   Choudhuri Gourdas G   Hegyi Péter P   te Morsche René H M RH   Drenth Joost P H JP   Truninger Kaspar K   Macek Milan M   Puhl Gero G   Witt Ulrike U   Schmidt Hartmut H   Büning Carsten C   Ockenga Johann J   Kage Andreas A   Groneberg David Alexander DA   Nickel Renate R   Berg Thomas T   Wiedenmann Bertram B   Bödeker Hans H   Keim Volker V   Mössner Joachim J   Teich Niels N   Sahin-Tóth Miklós M  

Nature genetics 20071202 1


Chronic pancreatitis is a persistent inflammatory disease of the pancreas, in which the digestive protease trypsin has a fundamental pathogenetic role. Here we have analyzed the gene encoding the trypsin-degrading enzyme chymotrypsin C (CTRC) in German subjects with idiopathic or hereditary chronic pancreatitis. Two alterations in this gene, p.R254W and p.K247_R254del, were significantly overrepresented in the pancreatitis group, being present in 30 of 901 (3.3%) affected individuals but only 21  ...[more]

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